Canagliflozin Continues Showing of Positive Renal Outcomes in CANVAS Data

Vlado Perkovic, PhD

According to new data from the CANVAS and CANVAS-R trials, canagliflozin (Invokana) was found to be associated with a reduced risk of sustained kidney function loss, as well as attenuated estimated glomerular filtration rate (eFGR) decline, and a reduction in albuminuria.

The reduction of albuminuria could suggest the possibility of a renoprotective effect from canagliflozin, as noted by lead author Vlado Perkovic, PhD, and colleagues, and the drug has previously shown positive signs related to renal outcomes. Perkovic told MD Mag in November 2017 that “data from the CANVAS Program clearly indicate better renal outcomes for people treated with canagliflozin, and suggest that this agent protects kidney function, in addition to providing previously presented cardiovascular benefits.”

In April 2018, the Janssen product showed a relative risk reduction of the composite endpoint (40% decline in eGFR, end-stage kidney disease, or renal death) by 47% in patients with preserved kidney function and 24% in patients with reduced kidney function.

Released at the American Diabetes Association’s 78th Annual Scientific Sessions, in Orlando, Florida, the new data on the sodium-glucose cotransporter-2 (SGLT2) inhibitor showed a slower annual decline in eGFR compared with placebo (slope difference 1.2 mL/min per 1.73 m² per year; 95% CI, 1.0 to 1.4) and as well as an 18% lower mean UACR (95% CI, 16 to 20).

Collected during 2 study periods—CANVAS, between November 17, 2009, and March 7, 2011; and CANVAS-R, between January 17, 2014, and May 29, 2015—the data included 10,142 patients with type 2 diabetes and a baseline mean eGFR of 76.5 mL/min per 1.73 m², and a median urinary albumin-to-creatinine ratio (UACR) of 12.3 mg/g. In total, 80% of the patients were being administered renin-angiotensin system blockade.

The total serious renal-related adverse events (AEs) were comparable between the groups, with those on canagliflozin reporting 2.5 per 1000 patient-years and placebo reporting 3.3 per 1000 patient-years (hazard ratio [HR], 0.76; 95% CI, 0.49 to 1.19).

The double-blind CANVAS-R trial randomized patients 1:1 to receive either canagliflozin in an initial dose of 100 mg, followed by optional up-titration to 300 mg post-week 13, or placebo. Meanwhile, the CANVAS trial participants were randomly assigned (1:1:1) to receive 300-mg canagliflozin, 100-mg canagliflozin, or matching placebo once daily.

The primary outcomes comprised of a composite of sustained and adjudicated doubling in serum creatinine, end-stage kidney disease, or death from renal causes; as well as the individual parts of the composite: annual reductions in eGFR and changes in UACR.

The study, “Canagliflozin and renal outcomes in type 2 diabetes: results from the CANVAS Program randomized clinical trials,” was published in The Lancet Diabetes & Endocrinology.

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